322
steroids 7 3 ( 2 0 0 8 ) 320–327
7.34–7.44 (m, 10H); 13C NMR (50 MHz, CDCl3) ı 14.1, 15.3, 22.7,
23.1, 27.1, 28.0, 28.2, 28.4, 29.4, 29.6, 29.7, 29.8, 30.4, 31.9, 34.2,
36.4, 39.6, 43.7, 49.6, 52.2, 69.8, 71.6, 89.6, 112.8, 114.5, 127.2,
127.3, 127.5, 127.7,127.8,128.3, 128.5,130.7, 137.4, 138.9, 139.2,
156.2
was quenched with
a saturated aqueous solution of
NaHCO3 (3 mL). Steroidal compounds were extracted with
dichloromethane (2× 5 mL). Organic layers were washed
with water, dried over MgSO4 and concentrated under
reduced pressure. The crude residue was purified by col-
umn chromatography using CH2Cl2/pentane (2:3) to yield the
deoxygenated product as a glass.
2.2.3. General procedure for catalytic hydrogenations as
exemplified by the preparation of
2.2.2.1. 3,17ˇ-Bisbenzyloxy-11ˇ-hexyl-estra-1,3,5(10)-triene
(7b). 77% yield (77 mg); glass; 1H NMR (300 MHz, CDCl3) ı
0.90 (t, 3H, J = 6.3 Hz), 1.03 (s, 3H), 1.22–1.72 (m, 17H), 1.88 (d,
1H, J = 12.3 Hz), 2.02 (m, 1H), 2.34–2.45 (m, 2H), 2.53 (dd, 1H,
J = 10.4 Hz and 4.2 Hz), 2.70–2.86 (m, 2H), 3.50 (t, 1H, J = 7.5 Hz),
4.61 (s, 2H), 5.05 (s, 2H), 6.72 (d, 1H, J = 2.3 Hz), 6.72 (dd, 1H,
J = 8.7 Hz and 2.3 Hz), 7.08 (d, 1H, J = 8.7 Hz), 7.32–7.47 (m, 10H);
13C NMR (75 MHz, CDCl3) ı 14.1, 15.1, 22.7, 23.1, 27.1, 28.0,
28.2, 28.3, 29.4, 30.4, 31.9, 34.2, 36.4, 39.6, 43.7, 49.6, 52.2, 69.9,
71.6, 89.6, 112.8, 114.5, 127.3, 127.7, 127.8, 128.2, 128.5, 130.7,
137.3, 138.9, 139.3, 156.2; MS (pos. ESI) (m/z): 575 (M + K)+, 559
(M + Na)+; [˛]2D5 55.2 (c 0.5, chloroform).
3,17ˇ-dihydroxy-11ˇ-hexyl-estra-1,3,5(10)-triene (8b)
To a solution of the bisbenzylated steroid 7b (0.045 mmol) in
MeOH (2 mL) was added 10% Pd/C (6 mg). The substrate was
hydrogenated overnight under 1 atm. The mixture was then
filtered on celite® and the filtrate was evaporated to afford the
product.
2.2.3.1. 3,17ˇ-Dihydroxy-11ˇ-hexyl-estra-1,3,5(10)-triene (8b).
98% yield (32 mg); white solid: mp 157.2–158.0 ◦C; 1H NMR
(300 MHz, CDCl3) ı 0.79–0.92 (m, 6H), 1.16–1.68 (m, 18H), 1.80 (d,
1H, J = 12.3 Hz), 1.97 (m, 1H), 2.19 (d, 1H, J = 13.5 Hz), 2.45–2.54
(m, 2H), 2.65–2.85 (m, 2H), 3.71 (t, 1H, J = 7.3 Hz), 6.55 (s, 1H),
6.64 (d, 1H, J = 8.3 Hz), 7.01 (d, 1H, J = 8.3 Hz); 13C NMR (75 MHz,
CDCl3) ı 14.1, 14.3, 22.7, 23.1, 27.0, 28.1, 28.2, 28.4, 30.2, 30.5,
31.9, 34.4, 36.2, 38.3, 43.5, 49.6, 52.0, 83.3, 113.1, 115.2, 127.9,
130.4, 139.2, 152.7; MS pos. ESI (m/z): 379 (M + Na)+; [˛]D25 67.4
(c 0.54, chloroform); (HRMS ESI Neg.) obsd 355.2637, calcd
355.2649 (+ 3.5 ppm) (C24H35O2).
2.2.2.2. 3,17ˇ-Bisbenzyloxy-11ˇ-(3,3,4,4,5,5,6,6,6-nonafluoro-
hexyl)-estra-1,3,5(10)-triene (7c). From 0.501 mmol of alcohol
6c (350 mg) in the presence of 15 equiv. of Et3SiH (2.6 mL)
and 30 equiv. of BF3.Et2O (5.1 mL). 80% yield (280 mg); glass;
1H NMR (300 MHz, CDCl3) ı 1.07 (s, 3H), 1.19–1.71 (m, 9H),
1.92–2.48 (m, 6H), 2.63 (dd, 1H, J = 10.4 Hz and 3.4 Hz), 2.76–2.93
(m, 2H), 3.53 (t, 1H, J = 7.5 Hz), 4.57–4.61–4.66–4.70 (AB system,
2H, J = 12.1 Hz), 5.08 (s, 2H), 6.77 (s, 1H), 6.86 (d, 1H, J = 8.6 Hz),
7.07 (d, 1H, J = 8.6 Hz), 7.34–7.43 (m, 10H); 19F NMR (188 MHz,
CDCl3) ı −81.5 (t, 3F, J = 10 Hz), −114.9 (m, 2F), −124.7 (m, 2F),
−126.5 (m, 2F); 13C NMR (75 MHz, CDCl3) ı 15.2, 19.1, 23.0, 26.9,
27.9, 29.7 (t, J = 22 Hz), 30.3, 34.1, 36.1, 39.3, 43.5, 49.4, 51.9, 69.9,
71.6, 89.4, 113.0, 114.9, 127.1, 127.3, 127.4, 127.5, 127.9, 128.3,
128.5, 129.6, 137.2, 139.0, 139.2, 156.5; MS (pos. ESI) (m/z): 721
(M + Na)+.
2.2.3.2. 3,17ˇ-Dihydroxy-11ˇ-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,
10,10-heptadecafluoro-decyl)-estra-1,3,5(10)-triene (8c). From
0.064 mmol of bisbenzylated steroid 7c (58 mg). 91% yield
(37 mg); white solid: mp 189.9–190.5 ◦C; 1H NMR (200 MHz,
CD3OD) ı 0.91 (s, 3H), 1.09–2.07 (m, 14H), 2.49–2.80 (m, 4H),
3.30 (m, 2H), 3.65 (t, 1H, J = 7.89 Hz), 6.50 (s, 1H), 6.58 (dd,
1H, J = 8.31 Hz and 2.20 Hz), 6.98 (d, 1H, J = 8.31 Hz); 19F NMR
(188 MHz, CD3OD) ı −78.9 (t, 3F, J = 10 Hz), −111.9 (m, 2F),
−119.5 (m, 6F), −120.3 (m, 2F), −121.1 (m, 2F), −123.8 (m, 2F);
13C NMR (50 MHz, CD3OD) ı 17.6, 22.8, 26.5, 30.7, 33.2, 33.4
(t, J = 21Hz), 33.8, 38.5, 39.8, 42.1, 47.1, 53.2, 55.5, 86.2, 116.9,
118.9, 130.9, 131.9, 142.7, 158.3; [˛]2D5 75.2 (c 0.38, methanol);
HRMS (ESI Neg.) obsd 717.1627, calcd 717.1661 (−4.8 ppm)
(C28H26O2F17).
2.2.2.3. 3,17ˇ-Bisbenzyloxy-11ˇ-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,
10,10-heptadecafluoro-decyl)-estra-1,3,5(10)-triene (7d). From
0.332 mmol of alcohol 6d (300 mg) in the presence of 15
equiv. of Et3SiH (0.8 mL) and 30 equiv. of BF3.Et2O (1.52 mL).
51% yield (151 mg); glass; 1H NMR (200 MHz, CDCl3) ı 1.01
(s, 3H), 1.27––1.67 (m, 10H), 1.87–2.43 (m, 4H), 2.60 (dd, 1H,
J = 10.0 Hz and 3.6 Hz), 2.80 (m, 2H), 3.49 (t, 1H, J = 7.5 Hz),
4.51–4.57–4.60–4.66 (AB system, 2H, J = 12.3 Hz), 5.04 (s, 2H),
6.72 (s, 1H), 6.80 (d, 1H, J = 8.5 Hz), 7.03 (d, 1H, J = 8.5 Hz),
7.29–7.43 (m, 10H); 19F NMR (188 MHz, CDCl3) ı −81.2 (t, 3F,
J = 10 Hz), −114.8 (m, 2F), −122.4 (m, 6F), −123.2 (m, 2F), −123.7
(m, 2F), −126.6 (m, 2F); 13C NMR (50 MHz, CDCl3) ı 15.2, 19.1,
23.1, 26.9, 27.9, 29.7 (t, J = 16 Hz), 29.8, 30.3, 34.1, 36.2, 39.4,
43.5, 49.4, 52.0, 69.9, 71.7, 89.4, 113.0, 114.9, 127.2, 127.4, 127.5,
127.9, 128.3, 128.5, 129.7, 137.2, 139.0, 139.2, 156.5; MS (ESI
pos.) (m/z): 921 (M + Na)+, 899 (M + H)+.
2.2.3.3. 3,17ˇ-Dihydroxy-11ˇ-(3,3,4,4,5,5,6,6,6-nonafluoro-
hexyl)-estra-1,3,5(10)-triene
(8d). From
0.329 mmol
of
bisbenzylated steroid 7d (230 mg). 72% yield (122 mg); white
solid: mp 213.0–213.6 ◦C; 1H NMR (300 MHz, CD3OD) ı 0.93 (s,
3H), 1.18–1.71 (m, 12H), 1.87 (d, 1H, J = 12.3 Hz), 2.02–2.56 (m,
5H), 2.63–2.84 (m, 2H), 3.68 (t, 1H, J = 7.9 Hz), 6.53 (s, 1H), 6.62
(dd, 1H, J = 8.46 Hz and 2.49 Hz), 6.98 (d, 1H, J = 8.46 Hz); 19F
NMR (188 MHz, CD3OD) ı −79.2 (t, 3F, J = 10 Hz), −112.1 (m, 2F),
−122.1 (m, 2F), −123.8 (m, 2F); 13C NMR (75 MHz, CD3OD) ı
15.2, 20.2, 24.0, 28.2, 30.7, 30.8 (t, J = 22 Hz), 31.3, 35.9, 37.3, 39.6,
44.6, 50.7, 53.0, 83.7, 114.4, 116.4, 128.4, 129.5, 140.2, 155.8;
MS pos. ESI (m/z): 541 (M + Na)+; [˛]D25 75.2 (c 0.38, methanol);
HRMS (ESI Neg.) obsd 517.1772, calcd 517.1789 (−3.3 ppm)
(C24H26O2F9).
2.2.2.4. 3,17ˇ-Bisbenzyloxy-11ˇ-decyl-estra-1,3,5(10)-triene
(7e). From 0.167 mmol of alcohol 6e (102 mg). 51% yield
(56 mg); glass; 1H NMR (200 MHz, CDCl3)
ı 0.90 (s, 3H,
J = 6.37 Hz), 1.02 (s, 3H), 1.27–1.68 (m, 26H), 1.85–2.05 (m, 2H),
2.32–2.55 (m, 2H), 2.76–2.84 (m, 2H), 3.48 (t, 1H, J = 7.56 Hz), 4.61
(s, 2H), 5.04 (s, 2H), 6.71–6.82 (m, 2H), 7.08 (d, 1H, J = 8.28 Hz),
2.2.3.4. 3,17ˇ-Dihydroxy-11ˇ-decyl-estra-1,3,5(10)-triene (8e).
From 0.094 mmol of bisbenzylated steroid 7e (56 mg). 80% yield
(37 mg); white solid: mp 146.4–147.2 ◦C; 1H NMR (200 MHz,